NYX-2925, A Novel N-methyl-D-aspartate Receptor Modulator: A First-in-Human, Randomized, Double-blind Study of Safety and Pharmacokinetics in Adults

  • Clin Transl Sci. 2019 Mar;12(2):164-171. doi: 10.1111/cts.12584.
David R Houck  1 ,  Laurel Sindelar  1 ,  Carlos R Sanabria  2 ,  Stephanie H Stanworth  2 ,  Maggie Krueger  1 ,  Mary Suh  1 ,  Torsten M Madsen  1
Affiliations
  • 1. Aptinyx Inc., Evanston, Illinois, USA.
  • 2. Spaulding Clinical Research, LLC, West Bend, Wisconsin, USA.
PMID: 30242962 DOI: 10.1111/cts.12584
Abstract

NYX-2925, a new chemical entity, acts as a co-agonist to glutamate at the N-methyl-D-aspartate receptor (NMDAR). At low concentrations of endogenous agonists (glycine/D-serine), NYX-2925 partially activates NMDARs, modulating neural pathways relevant for chronic pain. NYX-2925 is being developed for the treatment of chronic pain conditions, including painful diabetic peripheral neuropathy and fibromyalgia. In this first-in-human, phase I, single-ascending dose (50-1,200 mg) and multiple-ascending dose (150-900 mg) study, the safety, tolerability, and pharmacokinetics (PKs) of NYX-2925 were evaluated in 84 healthy adult volunteers. No safety concerns emerged, including no dissociative side effects. NYX-2925 exhibited dose-proportional PKs and minimal accumulation following once-daily dosing for 7 days. Cerebrospinal fluid (CSF) measurements confirmed that NYX-2925 crosses the blood brain barrier, with maximum CSF concentrations approximating 6-9% of maximum plasma concentrations at the same dose level. NYX-2925 was safe and well-tolerated in healthy volunteers, and the study results support the continued clinical development for chronic pain conditions.

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